*5.3.1 Pharmacotherapy of hyperglycemia*

The pharmacotherapy of hyperglycemia should be patient-centred, addressed to reduce glycemia and the overall CVR [53]. Metformin remains the first step of the treatment. It is initiated simultaneously with lifestyle optimization, from the diagnosis, and is continued throughout the treatment, associated with the other therapeutic classes. It is stopped in case of intolerance and at an eGFR <30 mL/ min/1.73 m<sup>2</sup> . For patients with established ASCVD or indicators of high ASCVD risk, established kidney disease, or heart failure, the guidelines recommend the medication with demonstrated CVD benefit, independent of the HbA1c value: SGLT-2 inhibitor (sodium-glucose cotransporter 2 inhibitor – empagliflozin, canagliflozin, dapagliflozin) or GLP-1RA (glucagon-like peptide 1 receptor agonist – semaglutide, liraglutide, dulaglutide, long-acting exenatide, lixisenatide) (**Table 2**) [12, 19, 53–59].

For patients without the conditions mentioned above, a second or third agent's choice as an add-on to metformin is based on CV safety, the effect on body weight, and avoidance of hypoglycemia. Sulfonylureas have controversial CV effects. To date, the ADVANCE study (Action in Diabetes and Vascular Disease: Preterax

